(a) Field of the Invention
This invention relates to a method of treatment of conditions such as bladder carcinoma, lung carcinoma, breast carcinoma, carcinoma of adrenal cortex, or pancreatic carcinoma by serotonin antagonists and primarily cyproheptadine.
(b) Description of Prior Art
There is a considerable number of studies on the ageing process, including the factors and agents responsible, and there are some suggestions to alleviate it. Some of the diseases often associated with old age include cancer, various heart diseases, arthritis, etc. In two articles which have appeared in 1982--P. S. Timiras et al, The Ageing Brain: Cellular and Molecular Mechanisms of Ageing in the Nervous system, edited by E. Giacobini et al, Raven Press, New York--Developing and Ageing Brain Serotonin Systems; and P. S .T. Timiras et al, Age and Aging (1982) 11, 73-88--there are discussions on the effect of serotonin on the ageing process. These studies have shown that serotonin accumulates in the central nervous system, with increasing age in a linear fashion, whereas its metabolite, melatonin, produced in the pineal gland decreases during aging.
The chemical cyproheptadine is a known serotonin antagonist and although other serotonin antagonists are known, the present discussion will be restricted to cyproheptadine because it is most available at present with least side effects, although the present invention is not restricted to applications of cyproheptadine. Numerous references describe the various medical uses of cyproheptadine. The following list is only partial:
(1) Studies of Mechanism of Cyproheptadine-induced Weight Gain in Human Subjects, John N. Stiel et al, Metabolism, March, 1970, 19(3) pp?.
(2) Experimental Study on Atherosclerosis, an Attempt at its Prevention and Treatment, Acta Pathol. Jap. February 1969, 19(1) pp. 15-43.
(3) A preliminary Report on BC-105: a new Antidepressant, Psychosomatics, January-February 1969, 10(1) pp. 51-2.
(4) More on Cyproheptadine in Cushing's Disease, New England J. Med. Mar. 10, 1977, 296(10) pp. 576-7.
It is worthwhile considering the potential therapeutic use of cyproheptadine against cancer because this disease continues to be a major cause of death in western society despite the massive research efforts. Cyproheptadine has been investigated in cancer not as a specific therapeutic agent against the growth and spread of the cancer cells but as a way of overcoming the anorexic effects of the disease by stimulating appetite.
The ageing process is characterized by a group of progressive diseases such as arteriosclerotic heart disease, cardiovascular accidents, hypertension, arthritis, diabetes; and an increase in age-related cancers. The serotonergic neurotransmitter system which is dominant in the central nervous system, and which directly effects the entire neuroendocrine system via the hypothalamic pituitary axis, is proposed in the prior art to be responsible for the ageing process for the following reasons.
By referring to the tables in the references of the Timiras et al mentioned above, it can be seen that serotonin promotes cystogenesis and causes general chronic inflammatory fibrotic changes, gradually leading to a replacement of normal tissues by chronic inflammatory debris-forming soars which in turn lead to increases in rigidity, decreased transport of nutrients and subsequent organ failure.
It is therefore believed that by administering an agent which is a serotonin-antagonist and which can cross the blood brain barrier to act within the central nervous system, this serotonin-antagonist would then act in effect as an anti-ageing substance and in that respect may also be used in the treatment of diseases of the aged, and other acute diseases.